- A general palladium-catalyzed cross-coupling of aryl fluorides and organotitanium (IV) reagents
-
Pd(OAc)2/1-[2-(di-tert-butylphosphanyl)phenyl]-4-methoxy-piperidine was demonstrated to effectively catalyze cross-coupling of aryl fluoride and aryl(alkyl) titanium reagent. Both electron-deficient and electron-rich aryl fluoride can react effectively with nucleophile and provide extensive functional groups tolerance. 2-Arylated product was realized by selective activation of the C–F bond. Graphic abstract: [Figure not available: see fulltext.].
- He, Xiao-Yun
-
p. 823 - 832
(2021/07/19)
-
- Improving the metabolic stability of antifungal compounds based on a scaffold hopping strategy: Design, synthesis, and structure-activity relationship studies of dihydrooxazole derivatives
-
L-amino alcohol derivatives exhibited high antifungal activity, but the metabolic stability of human liver microsomes in vitro was poor, and the half-life of optimal compound 5 was less than 5 min. To improve the metabolic properties of the compounds, the scaffold hopping strategy was adopted and a series of antifungal compounds with a dihydrooxazole scaffold was designed and synthesized. Compounds A33-A38 substituted with 4-phenyl group on dihydrooxazole ring exhibited excellent antifungal activities against C. albicans, C. tropicalis and C. krusei, with MIC values in the range of 0.03–0.25 μg/mL. In addition, the metabolic stability of compounds A33 and A34 in human liver microsomes in vitro was improved significantly, with the half-life greater than 145 min and the half-life of 59.1 min, respectively. Moreover, pharmacokinetic studies in SD rats showed that A33 exhibited favourable pharmacokinetic properties, with a bioavailability of 77.69%, and half-life (intravenous administration) of 9.35 h, indicating that A33 is worthy of further study.
- Cheng, Maosheng,Su, Xin,Sun, Nannan,Sun, Yin,Tian, Linfeng,Yin, Wenbo,Zhang, Chu,Zhao, Dongmei,Zhao, Liyu,Zhao, Shizhen,Zheng, Yang
-
-
- Green synthesis of biphenyl carboxylic acids via Suzuki–Miyaura cross-coupling catalyzed by a water-soluble fullerene-supported PdCl2 nanocatalyst
-
A green synthesis of variously substituted biphenyl carboxylic acids was achieved through Suzuki–Miyaura cross-coupling of a bromobenzoic acid with an aryl boronic acid using a water-soluble fullerene-supported PdCl2 nanocatalyst (C60-TEGs/ PdCl2). Yields of more than 90% were obtained at room temperature in 4 h using 0.05 mol% catalyst and 2 equiv. K2CO3.
- Liu, Wanyun,Zhou, Xiuming,Huo, Ping,Li, Jingbo,Mei, Guangquan
-
-
- Design, synthesis, and structure-activity relationship studies of L-amino alcohol derivatives as broad-spectrum antifungal agents
-
To discover broad spectrum antifungal agents, two strategies were applied, and a novel class of L-amino alcohol derivatives were designed and synthesized. 3-F substituted compounds 14i, 14n, 14s and 14v exhibited excellent antifungal activities with broad antifungal spectra against C. albicans and C. tropicalis, with MIC values in the range of 0.03–0.06 μg/mL, and against A. fumigatus and C. neoformans, with MIC values in the range of 1–2 μg/mL. Notably, Compounds 14i, 14n, 14s and 14v also displayed moderate activities against fluconazole-resistance strains 17# and CaR that were isolated from AIDS patients. Moreover, only compounds in the S-configuration showed antifungal activity. Preliminary mechanistic studies showed that the potent antifungal activity of compound 14v stemmed from inhibition of C. albicans CYP51. Compounds 14n and 14v were almost nontoxic to mammalian A549 cells, and their stability in human plasma was excellent.
- Zhao, Liyu,Tian, Linfeng,Sun, Nannan,Sun, Yin,Chen, Yixuan,Wang, Xinran,Zhao, Shizhen,Su, Xin,Zhao, Dongmei,Cheng, Maosheng
-
p. 374 - 385
(2019/06/05)
-
- Combating fluconazole-resistant fungi with novel β-azole-phenylacetone derivatives
-
A series of β-azole-phenylacetone derivatives with novel structures were designed and synthesized to combat the increasing incidence of susceptible fungal infections and drug-resistant fungal infections. The antifungal activity of the synthesized compounds was assessed against five susceptible strains and five fluconazole-resistant strains. Antifungal activity tests showed that most of the compounds exhibited excellent antifungal activities against five pathogenic strains with MIC values in the range of 0.03–1 μg/mL. Compounds with R1 = 3-F substituted and 15o and 15ae exhibited moderate antifungal activities against fluconazole-resistant strains 17# and CaR with MIC values in the range of 1–8 μg/mL. Compounds with R1 = H or 2-F (such as 15a, 15o, 15p) displayed moderate to good antifungal activity against fluconazole-resistant strains 632, 901 and 904 with MIC values in the range of 0.125–4 μg/mL. Notably, 15o and 15ae exhibited antifungal activity against five susceptible strains and five fluconazole-resistant strains. Preliminary mechanistic studies showed that the potent antifungal activity of compound 15ae stemmed from inhibition of C. albicans CYP51. Compounds 15o, 15z and 15ae were nearly nontoxic to mammalian A549 cells.
- Zhao, Liyu,Sun, Nannan,Tian, Linfeng,Sun, Yin,Chen, Yixuan,Wang, Xinran,Zhao, Shizhen,Su, Xin,Zhao, Dongmei,Cheng, Maosheng
-
-
- Method for synthesizing biphenylcarboxylic acid compound by using Suzuki coupling reaction
-
The invention provides a method for synthesizing a biphenylcarboxylic acid compound by using the Suzuki coupling reaction. According to the method, brominated aromatic hydrocarbon and arylboronic acidare used as raw materials, and water-soluble fullerene nanopalladium is used as a catalyst; and the equation of the Suzuki coupling reaction is as described in the specification. In the equation, R1and R2 represent substituents at different positions, may be acceptor or donor substituents, and may be monosubstitutents or polysubstitutent; and R1 and R2 may be identical or different groups. The water-soluble fullerene nanopalladium catalyst is cheap, easily available and environmentally friendly, and has high catalytic activity and stable properties. When the catalyst is used for catalysis ofthe Suzuki coupling reaction, conditions are mild, anhydrous anaerobic treatment and high-temperature treatment are not needed, and cost is low. The method can be applied to the industrial synthesisof non-steroidal anti-inflammatory drugs such as diphenylacetic acid and diflunisal.
- -
-
Paragraph 0027
(2018/09/21)
-
- Discovery of biphenyl imidazole derivatives as potent antifungal agents: Design, synthesis, and structure-activity relationship studies
-
Fungal infections have became a serious medical problem due to their high incidence and mortality. We describe the discovery and structure-activity relationships studies (SARs) of a series of novel biphenyl imidazole derivatives with excellent antifungal
- Zhao, Dongmei,Zhao, Shizhen,Zhao, Liyu,Zhang, Xiangqian,Wei, Peng,Liu, Chunchi,Hao, Chenzhou,Sun, Bin,Su, Xin,Cheng, Maosheng
-
p. 750 - 758
(2016/12/28)
-
- A highly efficient catalyst of a nitrogen-based ligand for the Suzuki coupling reaction at room temperature under air in neat water
-
Glycine, as a kind of commercially available and inexpensive ligand, is used to prepare an air-stable and water-soluble catalyst for the Suzuki-Miyaura reaction in our study. In the presence of 0.1% [PdCl2(NH 2CH2COOH)2] as the catalyst, extremely excellent catalytic activity towards the Suzuki-Miyaura coupling of aryl halides containing the carboxyl group with various aryl boronic acids is observed at room temperature under air in neat water. the Partner Organisations 2014.
- Liu, Shiwen,Lv, Meiyun,Xiao, Daoan,Li, Xiaogang,Zhou, Xiuling,Guo, Mengping
-
supporting information
p. 4511 - 4516
(2014/06/23)
-
- Oxidation of aldehydes to carboxylic acids in water catalyzed by cobalt(II) Schiff-base complex anchored to SBA-15/MCM-41
-
Cobalt(II) Schiff-base complexes were successfully anchored to SBA-15/MCM-41 and used as a catalyst for the oxidation of aldehydes to afford carboxylic acids in water under the action of hydrogen peroxide. Reaction conditions, such as different catalyst type, reaction temperature, reaction time, solvents media, and catalyst amount were studied systematically. High yield (up to 98%) of the process was reached. Such substrate-supported catalyst can be reused up to five times without significant loss of its catalytic activity which is not lower than 85%.
- Zhang, Wei-Dong,Xu, Lin-Xian,Shi, Wei,Wang, Chang-Chun,Hui, Yong-Hai,Xie, Zheng-Feng
-
p. 782 - 788
(2014/06/09)
-
- Palladium-catalyzed Suzuki cross-coupling of arylhydrazines via C-N bond cleavage
-
The first example of Pd-catalyzed Suzuki cross-coupling of readily available arylhydrazines with arylboronic acids via C-N bond cleavage was developed under air, affording various biaryl compounds with broad substrate applicability and moderate to good yields. Moreover, the rigorous exclusion of air/moisture is not required in these transformations. Thus, the protocol represents a simple and efficient procedure to access biaryl compounds.
- Peng, Zhimin,Hu, Gaobo,Qiao, Hongwei,Xu, Pengxiang,Gao, Yuxing,Zhao, Yufen
-
p. 2733 - 2738
(2014/04/17)
-
- SAR Studies on tetrahydroisoquinoline derivatives: The role of flexibility and bioisosterism to raise potency and selectivity toward P-glycoprotein
-
The development of P-glycoprotein (P-gp) ligands remains of considerable interest, mostly for investigating the proteins structure and transport mechanism. In recent years, many different generations of ligands have been tested for their ability to modulate P-gp activity. The aim of the present work is to perform SAR studies on tetrahydroisoquinoline derivatives in order to design potent and selective P-gp ligands. For this purpose, the effect of bioisosteric replacement and the role of flexibility have been investigated, and four series of tetrahydroisoquinoline ligands have been developed: (a) 2-aryloxazole bioisosteres, (b) elongated analogues, (c) 2H-chromene, and (d) 2-biphenyl derivatives. The results showed that both 2-biphenyl derivative 20b and elongated derivative 6g behaved as strong P-gp substrates. In conclusion, important aspects for developing potent and selective P-gp ligands have been highlighted, providing a solid starting point for further optimization.
- Capparelli, Elena,Zinzi, Laura,Cantore, Mariangela,Contino, Marialessandra,Perrone, Maria Grazia,Luurtsema, Gert,Berardi, Francesco,Perrone, Roberto,Colabufo, Nicola A.
-
p. 9983 - 9994
(2015/02/05)
-
- Enhanced aqueous Suzuki-Miyaura coupling allows site-specific polypeptide 18F-labeling
-
The excesses of reagents used in protein chemistry are often incompatible with the reduced or even inverse stoichiometries used for efficient radiolabeling. Analysis and screening of aqueous Pd(0) ligand systems has revealed the importance of a guanidine core and the discovery of 1,1-dimethylguanidine as an enhanced ligand for aqueous Suzuki-Miyaura cross-coupling. This novel Pd catalyst system has now allowed the labeling of small molecules, peptides, and proteins with the fluorine-18 prosthetic [ 18F]4-fluorophenylboronic acid. These findings now enable site-specific protein 18F-labeling under biologically compatible conditions using a metal-triggered reaction.
- Gao, Zhanghua,Gouverneur, Veronique,Davis, Benjamin G.
-
p. 13612 - 13615
(2013/10/01)
-
- A convenient chemical-microbial method for developing fluorinated pharmaceuticals
-
A significant proportion of pharmaceuticals are fluorinated and selecting the site of fluorine incorporation can be an important beneficial part a drug development process. Here we describe initial experiments aimed at the development of a general method of selecting optimum sites on pro-drug molecules for fluorination, so that metabolic stability may be improved. Several model biphenyl derivatives were transformed by the fungus Cunninghamella elegans and the bacterium Streptomyces griseus, both of which contain cytochromes P450 that mimic oxidation processes in vivo, so that the site of oxidation could be determined. Subsequently, fluorinated biphenyl derivatives were synthesised using appropriate Suzuki-Miyaura coupling reactions, positioning the fluorine atom at the pre-determined site of microbial oxidation; the fluorinated biphenyl derivatives were incubated with the microorganisms and the degree of oxidation assessed. Biphenyl-4-carboxylic acid was transformed completely to 4′-hydroxybiphenyl-4-carboxylic acid by C. elegans but, in contrast, the 4′-fluoro-analogue remained untransformed exemplifying the microbial oxidation-chemical fluorination concept. 2′-Fluoro- and 3′-fluoro-biphenyl-4-carboxylic acid were also transformed, but more slowly than the non-fluorinated biphenyl carboxylic acid derivative. Thus, it is possible to design compounds in an iterative fashion with a longer metabolic half-life by identifying the sites that are most easily oxidised by in vitro methods and subsequent fluorination without recourse to extensive animal studies.
- Bright, Tara V.,Dalton, Fay,Elder, Victoria L.,Murphy, Cormac D.,O'Connor, Neil K.,Sandford, Graham
-
p. 1135 - 1142
(2013/03/28)
-
- NOVEL NEUROTRYPSIN INHIBITORS
-
The invention relates to novel acylamino-hydroxy-benzamides of formula (I), wherein R1 is phenyl substituted by phenyl, phenoxy, phenylamino or heteroaryl, all optionally further substituted; bicyclic aryl, monocyclic heteroaryl substituted by
- -
-
Page/Page column 27
(2012/05/20)
-
- Microwave-assisted aqueous Suzuki coupling reactions catalyzed by ionic palladium(II) complexes
-
Suzuki coupling is one of the most powerful methods for the synthesis of biaryls. We have prepared and characterized a series of unsymmetrical sulfonated watersoluble Pd(II)-pyridyl imine complexes and investigated them as catalysts for the Suzuki cross-coupling reaction in water under microwave irradiation. The compounds proved to be effective catalysts. Springer Science+Business Media B.V. 2011.
- Hanhan, M. Emre,Senemoglu, Yetkin
-
experimental part
p. 109 - 116
(2012/08/28)
-
- An efficient protocol for the palladium-catalysed Suzuki-Miyaura cross-coupling
-
The palladacyclic catalyst precursor received by ortho-palladation of ([1,1′-biphenyl]-2-yloxy)diisopropyl-phosphine represents a highly active system for Suzuki-Miyaura cross-coupling reactions when used in neat water. An efficient, broadly applicable and sustainable aqueous protocol was developed using 2.5 eq. of Na2CO3 as base, allowing the reaction to be performed under air and at ambient temperature with Pd loadings of 0.04 mol%. Coupling products are obtained in high yields and excellent purity by simple filtration with no organic solvents needed throughout the whole reaction. A broad variety of functional groups are tolerated and a large number of substrates can be applied with this protocol. The crystal structure of the palladacyclic catalyst precursor is presented as well as investigations targeting the nature of catalyst activation and the active catalytic species.
- Marziale, Alexander N.,Jantke, Dominik,Faul, Stefan H.,Reiner, Thomas,Herdtweck, Eberhardt,Eppinger, Joerg
-
supporting information; experimental part
p. 169 - 177
(2011/03/23)
-
- Bis(imino)pyridine palladium(II) complexes as efficient catalysts for the Suzuki-Miyaura reaction in water
-
Bis(imino)pyridine palladium(II) complexes 3 and 4 of type [PdCl(L)PF 6] are found to be efficient catalysts for Suzuki-Miyaura reactions of aryl halides and arylboronic acids. The reactions proceed smoothly to generate the corresponding biaryl compounds in moderate to excellent yields. The synthesis of various fluorinated biphenyl derivatives was successfully achieved by the complex 4 catalyzed the Suzuki-Miyaura reaction in the presence of surfactants bearing a long alkyl chain. Copyright
- Liu, Ping,Yan, Mei,He, Ren
-
experimental part
p. 131 - 134
(2010/11/04)
-
- Amine Compounds
-
There is provided a compound exhibiting an activity of suppressing immune response with reduced adverse drug reactions, which compound is useful in the chemotherapy for preventing or treating, for example, a wide range of various autoimmune diseases including systemic erythematodes, chronic rheumatoid arthritis, Type I diabetes, inflammatory bowel disease, biliary cirrhosis, uveitis, multiple sclerosis or other disorders, or chronic inflammatory diseases, or cancers, lymphoma or leukemia, or resistance to organ or tissue transplantation or rejection against transplantation. Novel amine compounds having an S1P1/Edg1 receptor agonist effect, possible stereoisomers or racemic bodies of the compounds, or pharmacologically acceptable salts, hydrates or solvates of the compound, the stereoisomers or the racemic bodies, or prodrugs of the compounds, the stereoisomers, the racemic bodies, the salts, the hydrates or the solvates, are provided.
- -
-
Page/Page column 161
(2008/12/08)
-
- NOVEL DICARBOXYLIC ACID DERIVATIVES AS S1P1 RECEPTOR AGONISTS
-
The present invention relates to new compounds of formula (I) possessing agonistic activity at sphingosine-1 -phosphate (S1 P) receptors, their process of preparation and their use as immunosuppressive agents. The invention is also directed to pharmaceutical compositions containing these compounds and use of these compounds for treatment/prevention of immune mediated diseases and conditions or inflammatory diseases and conditions.
- -
-
-
- A liquid-phase approach to functionalized janus dendrimers: Novel soluble supports for organic synthesis
-
A new kind of functionalized Janus dendrimer has been synthesized via a liquid-phase approach, which could easily be purified using a simple precipitation method without the need for chromatographic separation. Their use for liquid-phase organic synthesis has been achieved in the Pd-catalyzed Suzuki coupling reactions, giving biaryl products in excellent yields after cleavage.
- Feng, Yu,He, Yan-Mei,Zhao, Li-Wen,Huang, Yi-Yong,Fan, Qing-Hua
-
p. 2261 - 2264
(2008/02/05)
-
- Microwave-promoted Suzuki-Miyaura coupling reactions in a cycloalkane-based thermomorphic biphasic system
-
Microwave-promoted Suzuki-Miyaura coupling reaction of aryl halides attached to a cycloalkane-soluble platform was accomplished in a cycloalkane-based thermomorphic biphasic system. Following irradiation and subsequent cooling, the monophasic reaction mix
- Hayashi, Kanako,Kim, Shokaku,Kono, Yusuke,Tamura, Mihoko,Chiba, Kazuhiro
-
p. 171 - 174
(2007/10/03)
-
- Synthesis of 18F-labelled biphenyls via SUZUKI cross-coupling with 4-[18F]fluoroiodobenzene
-
The SUZUKI reaction of organoboron compounds with 4-[18F] fluoroiodobenzene has been developed as a novel radiolabelling technique in 18F chemistry. The cross-coupling reaction of p-tolylboronic acid with 4-[18F]fluoroiodobenzene was used to screen different palladium complexes, bases and solvents. Optimized reaction conditions (Pd 2(dba)3, Cs2CO3, acetonitrile, 60°C for 5 min) were further applied to the synthesis of various 18F-labelled biphenyls bearing different functional groups. The reaction proceeded in excellent radiochemical yields of up to 94% within 5 min while showing good compatibility to many functional groups. Copyright
- Steiniger, Bjoern,Wuest, Frank R.
-
p. 817 - 827
(2007/10/03)
-
- Discovery of a potent inhibitor of the antiapoptotic protein Bcl-X L from NMR and parallel synthesis
-
The antiapoptotic proteins Bcl-xL and Bcl-2 play key roles in the maintenance of normal cellular homeostasis. However, their overexpression can lead to oncogenic transformation and is responsible for drug resistance in certain types of cancer. This makes Bcl-xL, and Bcl-2 attractive targets for the development of potential anticancer agents, Here we describe the structure-based discovery of a potent Bcl-xL inhibitor directed at a hydrophobic groove on the surface of the protein. This groove represents the binding site for BH3 peptides from proapoptotic Bcl-2 family members such as Bak and Bad. Application of NMR-based screening yielded an initial biaryl acid with an affinity (Kd) of ～300 μM for the protein. Following the classical "SAR by NMR" approach, a second-site ligand was identified that bound proximal to the first-site ligand in the hydrophobic groove. From NMR-based structural studies and parallel synthesis, a potent ligand was obtained, which binds to Bcl-xL with an inhibition constant (K i) of 36 ± 2 nM.
- Petros, Andrew M.,Dinges, Jurgen,Augeri, David J.,Baumeister, Steven A.,Betebenner, David A.,Bures, Mark G.,Elmore, Steven W.,Hajduk, Philip J.,Joseph, Mary K.,Landis, Shelley K.,Nettesheim, David G.,Rosenberg, Saul H.,Shen, Wang,Thomas, Sheela,Wang, Xilu,Zanze, Irini,Zhang, Haichao,Fesik, Stephen W.
-
p. 656 - 663
(2007/10/03)
-
- INDANE DERIVATES AS MUSCARINIC RECEPTOR AGONISTS
-
The present invention relates to compounds of Formula I: I which are agonists of the M-1 muscarinic receptor.
- -
-
-
- MUSCARINIC AGONISTS
-
The present invention relates to compounds of Formula (I): which are agonists of the M-1 muscarinic receptor.
- -
-
-
- MUSCARINIC AGONISTS
-
The present invention relates to compounds of Formula (I): which are agonists of the M-1 muscarinic receptor.
- -
-
-
- New carboxamide compounds having melanin concentrating hormone antagonistic activity, pharmaceutical preparations comprising these compounds and process for their manufacture
-
The present invention relates to carboxamide compounds of general formula I wherein the groups and residues A, B, W, X, Y, Z, R1, R2, R3 and k have the meanings given in claim 1. Moreover the invention relates to process for preparing the above mentioned carboxamides as well as pharmaceutical compositions containing at least one carboxamide according to the invention. In view of their MCH-receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and/or eating disorders, particularly obesity, bulimia, anorexia, hyperphagia and diabetes.
- -
-
Page/Page column 78
(2010/02/09)
-
- KETONES AND REDUCED KETONES AS THERAPEUTIC AGENTS FOR THE TREATMENT OF BONE CONDITIONS
-
The present invention pertains to certain ketones and reduced ketones and derivatives thereof which, inter alia, inhibit osteoclast survival, formation, and/or activity; and/or inhibit bone resorption, and more particularly to compounds of the formulae: (1) (2) wherein: Ar1 is independently a biphenyl, phenanthryl, fluorenyl, or carbazolyl, and is optionally substituted; Ralk is independently a C2-10alkylene group, and is optionally substituted; -ORO, if present, is independently -OH or -ORK; -ORK, if present, is independently selected from: -O-RK1; -O-C(=O)RK2; -O-C(=O)ORK3; -O-S(=O)2ORK4; Q is independently -OH or -OROT; wherein: -OROT, if present, is independently selected from: -O-RE1; -O-C(=O)-RE2; -O-C(=O)-O-RE3; -O-C(=O)-O-SO3RE4; -O-C(=O)-O-(CH2)n-COORE5; -O-C(=O)-(CH2)n-NRN1RN2; -O-C(=O)-(CH2)n-NH-C(=O)RE6; -O-C(=O)-(CH2)n-C(=O)-NRN3RN4; -O-P(=O)(ORE7)(ORE8); -O-RPA; RPA, if present, is an organic group which incorporates a phosphonic acid group; with the proviso that if -OROT is -O-RE1, then RE1 is not a phenyl group substituted with a sulfonyl group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, or prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit osteoclast survival, formation, and/or activity, and to inhibit conditions mediated by osteoclasts and/or characterised by bone resorption, in the treatment of bone disorders such as osteoporosis, rheumatoid arthritis, cancer associated bone disease, Paget's disease, aseptic loosening of prosthetic implants, and the like; and/or in the treatment of conditions associated with inflammation or activation of the immune system.
- -
-
-
- A novel anthracenyl tagged protecting group for "phase-switching" applications in parallel synthesis
-
A new "phase-switching" protecting group 1 that facilitates the parallel synthesis of carboxylic acids, esters, and carboxamides is described. Its use permits chemistries to be performed in solution, which may be conveniently monitored with conventional a
- Li, Xin,Abell, Chris,Ladlow, Mark
-
p. 4189 - 4194
(2007/10/03)
-
- N-acylsulfonamide apoptosis promoters
-
N-Benzoyl arylsulfonamides having the formula are BCL-Xl inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-Xl inhibiting compositions and methods of promoting apoptosis in a mammal.
- -
-
-
- Solid phase cross-coupling reaction of aryl(halo)silanes with 4-iodobenzoic acid
-
Aryl(alkyl)(halo)silanes undergo facile and efficient palladium catalyzed cross-coupling reaction with iodobenzoic acid tethered to the Wang resin. Acid cleavage releases unsymmetrical biaryl carboxylic acids with high conversions, purities and yields.
- Homsi, Fadi,Hosoi, Kazushi,Nozaki, Kyoko,Hiyama, Tamejiro
-
p. 208 - 216
(2007/10/03)
-
- Solid-phase cross-coupling reaction of aryl(fluoro)silanes with 4- iodobenzoic acid
-
Aryl(alkyl)(difluoro)silanes undergo a facile and efficient palladium- catalyzed cross-coupling reaction with iodobenzoic acid tethered to the Wang resin. Acid cleavage releases unsymmetrical biaryl carboxylic acids with high conversions, purities, and yields. (C) 2000 Elsevier Science Ltd.
- Homsi, Fadi,Nozaki, Kyoko,Hiyama, Tamejiro
-
p. 5869 - 5872
(2007/10/03)
-
- Pd(DIPHOS)2-catalyzed cross-coupling reactions of organoborons with free or polymer-bound aryl halides.
-
Bis[1,2-bis(diphenylphosphino)ethane]palladium(0) [Pd(DIPHOS)2] catalyzes cross-coupling reactions of free or polymer-bound aryl halides with organoboron compounds to produce biaryls in overall yields of 60-96%.
- De,Krogstad
-
p. 879 - 882
(2007/10/03)
-
- NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein
-
The E2 protein is required for the replication of human papillomaviruses (HPVs), which are responsible for anogenital warts and cervical carcinomas. Using an NMR-based screen we tested compounds for binding to the DNA-binding domain of the HPV-E2 protein. Three classes of compounds were identified which bound to two distinct sites on the protein. Biphenyl and biphenyl ether compounds containing a carboxylic acid bind to a site near the DNA recognition helix and inhibit the binding of E2 to DNA. Benzophenone- containing compounds which lack a carboxylic acid group bind to the β- barrel formed by the dimer interface and exhibit negligible effects on the binding of E2 to DNA. Structure-activity relationships from the biphenyl and biphenyl ether compounds were combined to produce a compound [5-(3'- (3'',5''-dichlorophenoxy)-phenyl)-2,4-pentadienoic acid] with an IC50 value of approximately 10 μM. This compound represents a useful lead for the development of antiviral agents that interfere with HPV replication and further illustrates the usefulness of the SAR by NMR method in the drug discovery process.
- Hajduk, Philip J.,Dinges, Jürgen,Miknis, Gregory F.,Merlock, Megan,Middleton, Tim,Kempf, Dale J.,Egan, David A.,Walter, Karl A.,Robins, Terry S.,Shuker, Suzy B.,Holzman, Thomas F.,Fesik, Stephen W.
-
p. 3144 - 3150
(2007/10/03)
-
- The Effects of Substituents on the Rate of Saponification of Biphenyl-4-carboxylates
-
Second-order rate constants have been measured for the saponification of methyl 2'-, 3'-, and 4'-substituted biphenyl-4-carboxylates at several temperatures in 85percent (w/w) methanol-water and activation parameters have been calculated.The Hammett equation applies very well to the saponification of 3'- and 4'-substituted biphenyl-4-carboxylates with ?-constants evaluated by the FMMF method.The effect of 2'-substituents is understandable in terms of ?-electron steric effects.
- Ananthakrishnanadar, Ponnambalanad.,Kannan, Nagarathnam
-
-
